New vaccine shows promise against typhoid and invasive salmonella in first human trial
Researchers at the University of Maryland School of Medicine’s Center for Vaccine Development and Global Health (CVD) have completed a successful Phase 1 clinical trial of a novel vaccine designed to protect against both typhoid fever and invasive non-typhoidal Salmonella--two major causes of illness and death among children in sub-Saharan Africa.
Results were published today in the journal Nature Medicine.
The investigational Trivalent Salmonella Conjugate Vaccine (TSCV) includes sugar molecules taken from the outer coating of the Salmonella typhi bacteria that cause typhoid and the two most common types of invasive Salmonella infections that are not associated with typhoid caused by Salmonella enterica. These sugars are attached to special proteins that help the body recognize and respond to the bacteria more effectively.
In the randomized, placebo-controlled Phase 1 trial, 22 healthy adults in the US received either a low dose (6.25 µg) or high dose (12.5 µg) of TSCV, or a placebo shot. The vaccine was found to be safe and well-tolerated, with only mild, short-lived injection site pain reported. Importantly, 100 percent of the vaccine recipients developed strong immune responses to all three polysaccharide components, while none of the placebo recipients did.
“These results are highly encouraging,” said study lead investigator Wilbur Chen, MD, MS, Professor of Medicine at UM School of Medicine and Chief of the Adult Clinical Studies section within CVD. “They show that TSCV has the potential to protect children in regions where both typhoid and salmonella are endemic and deadly.”
The vaccine also has the potential to protect Americans against Salmonella infections, one of the leading causes of foodborne illness. Every year, bacteria from raw or undercooked chicken and eggs and contaminated produce cause 1.35 million Salmonella infections in the US and more than 26,000 hospitalizations, according to the Centers for Disease Control and Prevention. The serotypes targeted by the TSCV vaccine are among the most common in US infections.
In fact, some study participants showed pre-existing antibody responses, suggesting prior exposure to the bacteria via foodborne illness. Such priming might have led to stronger and longer-lasting immunity in the adult study volunteers, though researchers remain optimistic about the vaccine’s effectiveness in infants and young children in endemic regions.
The vaccine triggered a strong and balanced immune response, including long-lasting antibodies—even at lower doses. It also activated a specific immune defense involving white blood cells that help clear infections, which hadn’t been seen before with one of the vaccine’s protein components. These findings suggest the vaccine could offer both gut-level and whole-body protection against Salmonella.
“These findings provide a strong foundation for future studies,” said study co-author Myron Levine, MD, DTPH, professor emeritus at UM School of Medicine and CVD founding director. “We plan to explore broader functional assays to identify correlates of protection and evaluate TSCV’s performance in young children—the population most vulnerable to these diseases.”
The vaccine was developed in collaboration with Bharat Biotech International Limited (BBIL), building on their WHO-prequalified Typbar TCV™ platform.
“In 2017, sub-Saharan Africa saw over 420,000 cases of Salmonella disease and 66,000 deaths, primarily among children,” said Mark T. Gladwin, MD, Dean of the UM School of Medicine. “Typhoid fever caused an additional 650,000 cases and nearly 9,000 deaths in the region. A single vaccine that protects against both could be a game-changer for global pediatric health.”
Reference:
Chen, W.H., Barnes, R.S., Sikorski, M.J. et al. A combination typhoid and non-typhoidal Salmonella polysaccharide conjugate vaccine in healthy adults: a randomized, placebo-controlled phase 1 trial. Nat Med (2025). https://doi.org/10.1038/s41591-025-04003-z
